ER Stress Induces Cleavage of Membrane-Bound ATF6 by the Same Proteases that Process SREBPs
Open accessAbstract
ATF6 is a membrane-bound transcription factor that activates genes in the endoplasmic reticulum (ER) stress response. When unfolded proteins accumulate in the ER, ATF6 is cleaved to release its cytoplasmic domain, which enters the nucleus. Here, we show that ATF6 is processed by Site-1 protease (S1P) and Site-2 protease (S2P), the enzymes that process SREBPs in response to cholesterol deprivation. ATF6 processing was blocked completely in cells lacking S2P and partially in cells lacking S1P. ATF6 processing required the RxxL and asparagine/proline motifs, known requirements for S1P and S2P processing, respectively. Cells lacking S2P failed to induce GRP78, an ATF6 target, in response to ER stress. ATF6 processing did not require SCAP, which is essential for SREBP processing. We conclude that S1P and S2P are required for the ER stress response as well as for lipid synthesis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Accumulation of lipid droplets is a common hallmark of ER stress.
“Accumulation of lipid droplets is a common hallmark of ER stress27,28.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [27]
Cites
Brown, M. S., & Goldstein, J. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80213-5 · Cited by 3,834 · see citing works
Self-citationHaze, K., Yoshida, H., Yanagi, H., Yura, T., & Mori, K. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.11.3787 · Cited by 2,073 · see citing works
[19] Receptor-mediated endocytosis of low-density lipoprotein in cultured cells
Goldstein, J. L., Basu, S. K., & Brown, M. S. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)98152-1 · Cited by 1,623 · see citing works
Self-citationAmino Acid Preferences for Specific Locations at the Ends of α Helices
Richardson, J. S., & Richardson, D. C. (1988) · Science · doi:10.1126/science.3381086 · Cited by 1,380 · see citing works
Regulated Intramembrane Proteolysis
Brown, M. S., Ye, J., Rawson, R. B., & Goldstein, J. L. (2000) · Cell · doi:10.1016/s0092-8674(00)80675-3 · Cited by 1,329 · see citing works
Self-citationYoshida, H., Haze, K., Yanagi, H., Yura, T., & Mori, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.50.33741 · Cited by 1,229 · see citing works
SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
Wang, X., Sato, R., Brown, M. S., Hua, X., & Goldstein, J. L. (1994) · Cell · doi:10.1016/0092-8674(94)90234-8 · Cited by 1,003 · see citing works
Self-citationActivation of ATF6 and an ATF6 DNA Binding Site by the Endoplasmic Reticulum Stress Response
Wang, Y., Shen, J., Arenzana, N., Tirasophon, W., Kaufman, R. J., & Prywes, R. (2000) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61473-0 · Cited by 617 · see citing works
Self-citationActivation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response.
Wang, Y., Shen, J., Arenzana, N., et al. (2000) · PubMed · doi:10.1074/jbc.m003322200 · Cited by 539 · see citing works
Sakai, J., Duncan, E. A., Rawson, R. B., Hua, X., Brown, M. S., & Goldstein, J. L. (1996) · Cell · doi:10.1016/s0092-8674(00)81304-5 · Cited by 528 · see citing works
Self-citationRawson, R. B., Zelenski, N. G., Nijhawan, D., Ye, J., Sakai, J., Hasan, M. T., Chang, T., Brown, M. S., & Goldstein, J. L. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80006-4 · Cited by 466 · see citing works
Self-citationSakai, J., Rawson, R. B., Espenshade, P. J., Cheng, D., Seegmiller, A. C., Goldstein, J. L., & Brown, M. S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80150-1 · Cited by 405 · see citing works
Self-citationSignal Transduction From the Endoplasmic Reticulum to the Cell Nucleus
Pahl, H. L. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.3.683 · Cited by 350 · see citing works
Regulated Step in Cholesterol Feedback Localized to Budding of SCAP from ER Membranes
Nohturfft, A., Yabe, D., Goldstein, J. L., Brown, M. S., & Espenshade, P. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00037-4 · Cited by 347 · see citing works
Self-citationTransport-Dependent Proteolysis of SREBP
DeBose‐Boyd, R. A., Brown, M. S., Li, W., Nohturfft, A., Goldstein, J. L., & Espenshade, P. J. (1999) · Cell · doi:10.1016/s0092-8674(00)81668-2 · Cited by 326 · see citing works
Self-citationNohturfft, A., DeBose‐Boyd, R. A., Scheek, S., Goldstein, J. L., & Brown, M. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11235 · Cited by 244 · see citing works
Self-citationSakai, J., Nohturfft, A., Goldstein, J. L., & Brown, M. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5785 · Cited by 222 · see citing works
Self-citationHua, X., Sakai, J., Brown, M. S., & Goldstein, J. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.17.10379 · Cited by 209 · see citing works
Self-citationEspenshade, P. J., Cheng, D., Goldstein, J. L., & Brown, M. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.32.22795 · Cited by 179 · see citing works
Self-citationDuncan, E. A., Brown, M. S., Goldstein, J. L., & Sakai, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.19.12778 · Cited by 177 · see citing works
Self-citationRawson, R. B., DeBose‐Boyd, R. A., Goldstein, J. L., & Brown, M. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.40.28549 · Cited by 171 · see citing works
Self-citationLoss of transcriptional repression of three sterol-regulated genes in mutant hamster cells
Metherall, J. E., Goldstein, J. L., Luskey, K. L., & Brown, M. S. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84879-2 · Cited by 159 · see citing works
Self-citationDuncan, E. A., Davé, U. P., Sakai, J., Goldstein, J. L., & Brown, M. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17801 · Cited by 157 · see citing works
Self-citationYe, J., Davé, U. P., Grishin, N. V., Goldstein, J. L., & Brown, M. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5123 · Cited by 143 · see citing works
Self-citationZelenski, N. G., Rawson, R. B., Brown, M. S., & Goldstein, J. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.31.21973 · Cited by 114 · see citing works
Self-citationRawson, R. B., Cheng, D., Brown, M. S., & Goldstein, J. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.43.28261 · Cited by 95 · see citing works
Self-citationA turn propensity scale for transmembrane helices
Monné, M., Hermansson, M., & von HEIJNE, G. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2657 · Cited by 90 · see citing works
Hasan, M. T., Chang, C. C. Y., & Chang, T. (1994) · Somatic Cell and Molecular Genetics · doi:10.1007/bf02254759 · Cited by 54 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Signal integration in the endoplasmic reticulum unfolded protein response
Ron, D., & Walter, P. (2007) · Nature reviews. Molecular cell biology · doi:10.1038/nrm2199 · Cited by 6,499 · see citing works
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Walter, P., & Ron, D. (2011) · Science · doi:10.1126/science.1209038 · Cited by 5,893 · see citing works
Yoshida, H., Matsui, T., Yamamoto, A., Okada, T., & Mori, K. (2001) · Cell · doi:10.1016/s0092-8674(01)00611-0 · Cited by 4,054 · see citing works
THE MAMMALIAN UNFOLDED PROTEIN RESPONSE
Schröder, M., & Kaufman, R. J. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.074134 · Cited by 3,035 · see citing works
Roles of CHOP/GADD153 in endoplasmic reticulum stress
Oyadomari, S., & Mori, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401373 · Cited by 2,833 · see citing works
IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
Calfon, M. A., Zeng, H., Urano, F., Till, J. H., Hubbard, S. R., Harding, H. P., Clark, S. G., & Ron, D. (2002) · Nature · doi:10.1038/415092a · Cited by 2,826 · see citing works
Mechanisms, regulation and functions of the unfolded protein response
Hetz, C., Zhang, K., & Kaufman, R. J. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0250-z · Cited by 2,666 · see citing works
Endoplasmic reticulum stress: cell life and death decisions
Xu, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26373 · Cited by 2,260 · see citing works
Lee, A., Iwakoshi, N. N., & Glimcher, L. H. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7448-7459.2003 · Cited by 2,041 · see citing works
From endoplasmic-reticulum stress to the inflammatory response
Zhang, K., & Kaufman, R. J. (2008) · Nature · doi:10.1038/nature07203 · Cited by 2,010 · see citing works
Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities
Kim, I., Xu, W., & Reed, J. C. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2755 · Cited by 1,816 · see citing works
Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, É., Shyy, J. Y.-J., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.009 · Cited by 1,788 · see citing works
ER stress and the unfolded protein response
Schröder, M., & Kaufman, R. J. (2004) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.06.056 · Cited by 1,750 · see citing works
The Role of Endoplasmic Reticulum Stress in Human Pathology
Oakes, S. A., & Papa, F. R. (2014) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104649 · Cited by 1,589 · see citing works
Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Cycle or a Double-Edged Sword?
Malhotra, J., & Kaufman, R. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1782 · Cited by 1,507 · see citing works
Cellular Stress Responses: Cell Survival and Cell Death
Fulda, S., Gorman, A. M., Hori, O., & Samali, A. (2010) · International Journal of Cell Biology · doi:10.1155/2010/214074 · Cited by 1,508 · see citing works
Shen, J., Chen, X., Hendershot, L. M., & Prywes, R. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00203-4 · Cited by 1,461 · see citing works
Self-citationIRE1 Signaling Affects Cell Fate During the Unfolded Protein Response
Lin, J. H., Li, H., Yasumura, D., Cohen, H., Zhang, C., Panning, B., Shokat, K., Lavail, M., & Walter, P. (2007) · Science · doi:10.1126/science.1146361 · Cited by 1,435 · see citing works
Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease
Cao, S. S., & Kaufman, R. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5851 · Cited by 1,304 · see citing works
A trip to the ER: coping with stress
Rutkowski, D. T., & Kaufman, R. J. (2003) · Trends in Cell Biology · doi:10.1016/j.tcb.2003.11.001 · Cited by 1,364 · see citing works
Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond
Lee, P., Chandel, N. S., & Simon, M. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0227-y · Cited by 1,272 · see citing works
Coupling endoplasmic reticulum stress to the cell death program
Rao, R. V., Ellerby, H. M., & Bredesen, D. E. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401378 · Cited by 1,208 · see citing works
Seidah, N. G., Benjannet, S., Wickham, L., Marcinkiewicz, J., Jasmin, S. B., Stifani, S., Basak, A., Prat, A., & Chrétien, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0335507100 · Cited by 1,191 · see citing works
The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus
Eizirik, D. L., Cardozo, A. K., & Cnop, M. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0015 · Cited by 1,173 · see citing works
Endoplasmic reticulum stress in liver disease
Malhi, H., & Kaufman, R. J. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.11.005 · Cited by 1,178 · see citing works
SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology
Shimano, H., & Sato, R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.91 · Cited by 1,174 · see citing works
Hu, H., Tian, M., Ding, C., & Yu, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03083 · Cited by 1,140 · see citing works
The impact of the endoplasmic reticulum protein-folding environment on cancer development
Wang, M., & Kaufman, R. (2014) · Nature Reviews. Cancer · doi:10.1038/nrc3800 · Cited by 1,081 · see citing works
Yoshida, H. (2007) · The FEBS Journal · doi:10.1111/j.1742-4658.2007.05639.x · Cited by 1,086 · see citing works
A mitochondrial specific stress response in mammalian cells
Zhao, Q., Wang, J., Levichkin, I. V., Stasinopoulos, S., Ryan, M. T., & Hoogenraad, N. J. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf445 · Cited by 1,026 · see citing works
Yamamoto, K., Sato, T., Matsui, T., Sato, M., Okada, T., Yoshida, H., Harada, A., & Mori, K. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.07.018 · Cited by 974 · see citing works
Lee, K., Tirasophon, W., Shen, X., Michalak, M., Prywes, R., Okada, T., Yoshida, H., Mori, K., & Kaufman, R. J. (2002) · Genes & Development · doi:10.1101/gad.964702 · Cited by 1,055 · see citing works
Self-citationEndoplasmic reticulum stress: molecular mechanism and therapeutic targets
Chen, X., Shi, C., He, M., Xiong, S., & Xia, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01570-w · Cited by 1,072 · see citing works
Self-citationEndoplasmic reticulum stress signalling-from basic mechanisms to clinical applications
Almanza, A., Carlesso, A., Chintha, C., Creedican, S., Doultsinos, D., Leuzzi, B., Luís, A., McCarthy, N., Montibeller, L., More, S., et al. (2019) · The FEBS Journal · doi:10.1111/febs.14608 · Cited by 1,034 · see citing works
The glucose-regulated proteins: stress induction and clinical applications
Lee, A. S. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01908-9 · Cited by 1,033 · see citing works
Orchestrating the unfolded protein response in health and disease
Kaufman, R. J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216886 · Cited by 1,015 · see citing works
Autophagy Counterbalances Endoplasmic Reticulum Expansion during the Unfolded Protein Response
Bernales, S., McDonald, K. L., & Walter, P. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040423 · Cited by 1,009 · see citing works
The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress
Lee, A. S. (2005) · Methods · doi:10.1016/j.ymeth.2004.10.010 · Cited by 994 · see citing works
The endoplasmic reticulum and the unfolded protein response
Malhotra, J. D., & Kaufman, R. J. (2007) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2007.09.003 · Cited by 984 · see citing works
Endoplasmic Reticulum Stress Signaling in Disease
Marciniak, S. J., & Ron, D. (2006) · Physiological Reviews · doi:10.1152/physrev.00015.2006 · Cited by 948 · see citing works
Measuring ER Stress and the Unfolded Protein Response Using Mammalian Tissue Culture System
Oslowski, C. M., & Urano, F. (2011) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-385114-7.00004-0 · Cited by 925 · see citing works
Transcriptional and Translational Control in the Mammalian Unfolded Protein Response
Harding, H. P., Calfon, M. A., Urano, F., Novoa, I., & Ron, D. (2002) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.18.011402.160624 · Cited by 918 · see citing works
From acute ER stress to physiological roles of the Unfolded Protein Response
Wu, J., & Kaufman, R. J. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401840 · Cited by 868 · see citing works
The biology and therapeutic targeting of the proprotein convertases
Seidah, N. G., & Prat, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3699 · Cited by 819 · see citing works
Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response.
Zhang, K.-Z., Shen, X., Wu, J., Sakaki, K., Saunders, T., Rutkowski, D., Back, S., & Kaufman, R. J. (2006) · Cell · doi:10.1016/j.cell.2005.11.040 · Cited by 840 · see citing works
Hai, T., & Hartman, M. G. (2001) · Gene · doi:10.1016/s0378-1119(01)00551-0 · Cited by 808 · see citing works
Endoplasmic reticulum stress in disease pathogenesis.
Lin, J. H., Walter, P., & Yen, T. S. B. (2008) · Annual Review of Pathology · doi:10.1146/annurev.pathmechdis.3.121806.151434 · Cited by 830 · see citing works
Rutkowski, D. T., Arnold, S. M., Miller, C. N., Wu, J., Li, J., Gunnison, K. M., Mori, K., Akha, A. A. S., Raden, D. L., & Kaufman, R. J. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040374 · Cited by 804 · see citing works
Patil, C., & Walter, P. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00219-2 · Cited by 779 · see citing works
Rouschop, K. M. A., van den Beucken, T., Dubois, L., Niessen, H., Bussink, J., Savelkouls, K., Keulers, T., Mujcic, H., Landuyt, W., Voncken, J. W., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40027 · Cited by 829 · see citing works
Kammoun, H. L., Chabanon, H., Hainault, I., Luquet, S., Magnan, C., Koike, T., Ferré, P., & Foufelle, F. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37007 · Cited by 732 · see citing works
Regulation of apoptosis by endoplasmic reticulum pathways
Breckenridge, D. G., Germain, M., Mathai, J. P., Nguyen, M., & Shore, G. C. (2003) · Oncogene · doi:10.1038/sj.onc.1207108 · Cited by 742 · see citing works
Endoplasmic Reticulum Stress Sensing in the Unfolded Protein ResponsePreprint
Gardner, B. M., Pincus, D., Gotthardt, K., Gallagher, C. M., & Walter, P. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a013169 · Cited by 725 · see citing works
The role of the unfolded protein response in tumour development: friend or foe?
Ma, Y., & Hendershot, L. M. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1505 · Cited by 712 · see citing works
Shen, X., Ellis, R. E., Lee, K., Liu, C.-Y., Yang, K., Solomon, A., Yoshida, H., Morimoto, R., Kurnit, D. M., Mori, K., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00612-2 · Cited by 703 · see citing works
Werstuck, G. H., Lentz, S. R., Dayal, S., Hossain, G. S., Sood, S. K., Shi, Y., Zhou, J., Maeda, N., Krisans, S. K., Malinow, M. R., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11596 · Cited by 702 · see citing works
Ma, Y., Brewer, J. W., Diehl, J. A., & Hendershot, L. M. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00234-6 · Cited by 689 · see citing works
ATF6α Optimizes Long-Term Endoplasmic Reticulum Function to Protect Cells from Chronic Stress
Wu, J., Rutkowski, D. T., Dubois, M., Swathirajan, J., Saunders, T. L., Wang, J., Song, B., Yau, G. D.-Y., & Kaufman, R. J. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.07.005 · Cited by 680 · see citing works
Cellular response to endoplasmic reticulum stress: a matter of life or death
Boyce, M., & Yuan, J. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401817 · Cited by 681 · see citing works
A Time-Dependent Phase Shift in the Mammalian Unfolded Protein Response
Yoshida, H., Matsui, T., Hosokawa, N., Kaufman, R. J., Nagata, K., & Mori, K. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00022-4 · Cited by 675 · see citing works
Endoplasmic reticulum stress responses
Schröder, M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7383-5 · Cited by 669 · see citing works
The endoplasmic reticulum stress response in immunity and autoimmunity
Todd, D. J., Lee, A., & Glimcher, L. H. (2008) · Nature reviews. Immunology · doi:10.1038/nri2359 · Cited by 621 · see citing works
The Endoplasmic Reticulum: Folding, Calcium Homeostasis, Signaling, and Redox Control
Görlach, A., Klappa, P., & Kietzmann, T. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.1391 · Cited by 616 · see citing works
Wang, M., Wey, S., Zhang, Y., Ye, R., & Lee, A. S. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2485 · Cited by 611 · see citing works
A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and Oxidative Stress
Chaudhari, N., Talwar, P., Parimisetty, A., Lefebvre d’Hellencourt, C., & Ravanan, P. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00213 · Cited by 600 · see citing works
The unfolded protein response in nutrient sensing and differentiation
Kaufman, R. J., Scheuner, D. L., Schröder, M., Shen, X., Lee, K., Liu, C. Y., & Arnold, S. M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm829 · Cited by 607 · see citing works
Proteasome inhibitors disrupt the unfolded protein response in myeloma cells
Lee, A., Iwakoshi, N. N., Anderson, K. C., & Glimcher, L. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1334037100 · Cited by 600 · see citing works
Regulation of Sterol Synthesis in Eukaryotes
Espenshade, P. J., & Hughes, A. L. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130315 · Cited by 593 · see citing works
Signaling the Unfolded Protein Response from the Endoplasmic Reticulum
Zhang, K., & Kaufman, R. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400008200 · Cited by 580 · see citing works
Zhang, K., & Kaufman, R. J. (2006) · Neurology · doi:10.1212/01.wnl.0000192306.98198.ec · Cited by 580 · see citing works
γ-Secretase: proteasome of the membrane?
Kopan, R., & Ilagan, M. X. G. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1406 · Cited by 554 · see citing works
Endoplasmic Reticulum and the Unfolded Protein Response
Bravo, R., Parra, V., Gatica, D., Rodriguez, A. E., Torrealba, N., Paredes, F., Wang, Z. V., Antonio Zorzano, A., Hill, J. A., Jaimovich, E., et al. (2013) · International review of cytology · doi:10.1016/b978-0-12-407704-1.00005-1 · Cited by 549 · see citing works
Intracellular Signaling by the Unfolded Protein Response
Bernales, S., Papa, F. R., & Walter, P. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.122303.120200 · Cited by 543 · see citing works
Arroyave-Ospina, J. C., Wu, Z., Geng, Y., & Moshage, H. J. (2021) · Antioxidants · doi:10.3390/antiox10020174 · Cited by 531 · see citing works
Shuda, M., Kondoh, N., Imazeki, N., Tanaka, K., Okada, T., Mori, K., Hada, A., Arai, M., Wakatsuki, T., Matsubara, O., et al. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(03)00029-1 · Cited by 520 · see citing works
Pharmacological targeting of endoplasmic reticulum stress in disease
Marciniak, S., Chambers, J. E., & Ron, D. (2021) · Nature reviews. Drug discovery · doi:10.1038/s41573-021-00320-3 · Cited by 1 · see citing works
Okada, T., Yoshida, H., Akazawa, R., Negishi, M., & Mori, K. (2002) · Biochemical Journal · doi:10.1042/bj20020391 · Cited by 522 · see citing works
Endoplasmic reticulum stress-mediated apoptosis in pancreatic β-cells
Oyadomari, S., Araki, E., & Mori, M. (2002) · APOPTOSIS · doi:10.1023/a:1016175429877 · Cited by 517 · see citing works
Endoplasmic reticulum stress in immunity.
Bettigole, S., & Glimcher, L. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112116 · Cited by 491 · see citing works
Cancer and ER stress: Mutual crosstalk between autophagy, oxidative stress and inflammatory response
Lin, Y., Jiang, M. H., Chen, W., Zhao, T., & Wei, Y. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109249 · Cited by 505 · see citing works
The Unfolded Protein Response: An Overview
Read, A. M., & Schröder, M. (2021) · Biology · doi:10.3390/biology10050384 · Cited by 503 · see citing works
APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
Blanchard, J. W., Akay, L. A., Davila-Velderrain, J., von Maydell, D., Mathys, H., Davidson, S. M., Effenberger, A., Chen, C.-Y., Maner-Smith, K., Hajjar, I., et al. (2022) · Nature · doi:10.1038/s41586-022-05439-w · Cited by 493 · see citing works
“Accumulation of lipid droplets is a common hallmark of ER stress 27,28 .”
BackgroundAdachi, Y., Yamamoto, K., Okada, T., Yoshida, H., Harada, A., & Mori, K. (2008) · Cell Structure and Function · doi:10.1247/csf.07044 · Cited by 492 · see citing works
Chen, X., Shen, J., & Prywes, R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110636200 · Cited by 489 · see citing works
Self-citationEndoplasmic Reticulum Stress: Signaling the Unfolded Protein Response
Lai, E., Teodoro, T., & Volchuk, A. (2007) · Physiology · doi:10.1152/physiol.00050.2006 · Cited by 478 · see citing works
Deng, Y., Humbert, S., Liu, J., Srivastava, R., Rothstein, S. J., & Howell, S. H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102117108 · Cited by 476 · see citing works
A transgenic mouse model for monitoring endoplasmic reticulum stress
Iwawaki, T., Akai, R., Kohno, K., & Miura, M. (2003) · Nature Medicine · doi:10.1038/nm970 · Cited by 472 · see citing works
Liu, J., Srivastava, R., Che, P., & Howell, S. H. (2007) · The Plant Journal · doi:10.1111/j.1365-313x.2007.03195.x · Cited by 470 · see citing works
A Conserved SREBP-1/Phosphatidylcholine Feedback Circuit Regulates Lipogenesis in Metazoans
Walker, A. K., Jacobs, R. L., Watts, J. L., Rottiers, V., Jiang, K., Finnegan, D. M., Shioda, T., Hansen, M., Yang, F., Niebergall, L. J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.09.045 · Cited by 466 · see citing works
Ma, Y., & Hendershot, L. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301107200 · Cited by 458 · see citing works
Liu, J., Srivastava, R., Che, P., & Howell, S. H. (2007) · The Plant Cell · doi:10.1105/tpc.106.050021 · Cited by 460 · see citing works
ER chaperone functions during normal and stress conditions
Ma, Y., & Hendershot, L. M. (2004) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2003.08.007 · Cited by 440 · see citing works
The ER function BiP is a master regulator of ER function.
Hendershot, L. M. (2004) · PubMed · Cited by 439 · see citing works
Yamamoto, K. (2004) · The Journal of Biochemistry · doi:10.1093/jb/mvh122 · Cited by 438 · see citing works
Misfolded proteins, endoplasmic reticulum stress and neurodegeneration
Rao, R. V., & Bredesen, D. E. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.09.012 · Cited by 431 · see citing works
Redox signaling and unfolded protein response coordinate cell fate decisions under ER stress
Zhang, Z., Zhang, L., Zhou, L., Lei, Y., Zhang, Y., & Huang, C. (2018) · Redox Biology · doi:10.1016/j.redox.2018.11.005 · Cited by 422 · see citing works
ER stress-induced inflammation: does it aid or impede disease progression?
Garg, A. D., Kaczmarek, A., Krysko, O., Vandenabeele, P., Krysko, D., & Agostinis, P. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.06.010 · Cited by 429 · see citing works
Endoplasmic Reticulum Stress Signaling in Cancer Cells
Oakes, S. A. (2020) · The American Journal of Pathology · doi:10.1016/j.ajpath.2020.01.010 · Cited by 397 · see citing works
Yoshida, H., Oku, M., Suzuki, M., & Mori, K. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200508145 · Cited by 417 · see citing works
Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells
Fonseca, S. G., Ishigaki, S., Oslowski, C. M., Lu, S., Lipson, K. L., Ghosh, R., Hayashi, E., Ishihara, H., Oka, Y., Permutt, M. A., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39678 · Cited by 412 · see citing works
- Authors
- Ye, J., Rawson, R. B., Komuro, R., Chen, X., Davé, U. P., Prywes, R., Brown, M. S., & Goldstein, J. L.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Columbia University (US)
- Corresponding author
- Brown, Michael S
- Goldstein, Joseph L
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 6
- Issue
- 6
- Pages
- 1355-1364
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2127639686
- Cited by
- 1,871
- References
- 27
- Citations by year
- 2026: 60 · 2025: 58 · 2024: 108 · 2023: 98 · 2022: 87 · 2021: 102 · 2020: 93 · 2019: 89 · 2018: 89 · 2017: 69 · 2016: 83 · 2015: 80 · 2014: 58 · 2013: 96 · 2012: 81
- FWCI
- 16.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- National Cancer Institute (R01CA050329, CA 50329)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- ATF6, endoplasmic reticulum stress, site-1 protease, site-2 protease, proteolytic cleavage, GRP78, SCAP, lipogenesis, unfolded protein response
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, DNA-Binding Proteins, Endoplasmic Reticulum, Heat-Shock Proteins, Humans, Intracellular Membranes, Membrane Proteins, Molecular Sequence Data, Mutation, Endopeptidases, Protein Binding, Protein Processing, Post-Translational, RNA, Messenger, Serine Endopeptidases, Transcription Factors, Transcription, Genetic, Tunicamycin, Immunoblotting, Sequence Alignment, Molecular Chaperones, Thapsigargin, Amino Acid Motifs, CCAAT-Enhancer-Binding Proteins, Proprotein Convertases, Intracellular Signaling Peptides and Proteins, Activating Transcription Factor 6, Sterol Regulatory Element Binding Protein 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review